Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes
© 2022. The Author(s)..
AIMS/HYPOTHESIS: B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes.
METHODS: Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice.
RESULTS: B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet CD19+CD138- and CD19+CD138+ B cell subsets, the latter of which is known to have enriched autoreactivity during diabetes development. On localisation to pancreatic islets, compared with CD138- B cells, CD138+ B cells overexpress genes associated with adhesion molecules and growth factors. Their shared signature consists of gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with IFN signalling pathways, proinflammatory cytokines and Toll-like receptor (TLR) activation. Finally, abundant TLR7 expression was detected in islet B cells and was enhanced specifically in CD138+ B cells.
CONCLUSIONS/INTERPRETATION: Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:66 |
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| Enthalten in: |
Diabetologia - 66(2023), 3 vom: 12. März, Seite 551-566 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Boldison, Joanne [VerfasserIn] |
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| Links: |
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| Themen: |
Autoimmunity |
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| Anmerkungen: |
Date Completed 03.02.2023 Date Revised 22.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00125-022-05839-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350202125 |
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| 100 | 1 | |a Boldison, Joanne |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes |
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| 500 | |a Date Completed 03.02.2023 | ||
| 500 | |a Date Revised 22.03.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a AIMS/HYPOTHESIS: B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes | ||
| 520 | |a METHODS: Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice | ||
| 520 | |a RESULTS: B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet CD19+CD138- and CD19+CD138+ B cell subsets, the latter of which is known to have enriched autoreactivity during diabetes development. On localisation to pancreatic islets, compared with CD138- B cells, CD138+ B cells overexpress genes associated with adhesion molecules and growth factors. Their shared signature consists of gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with IFN signalling pathways, proinflammatory cytokines and Toll-like receptor (TLR) activation. Finally, abundant TLR7 expression was detected in islet B cells and was enhanced specifically in CD138+ B cells | ||
| 520 | |a CONCLUSIONS/INTERPRETATION: Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Autoimmunity | |
| 650 | 4 | |a B cells | |
| 650 | 4 | |a Pancreatic islets | |
| 650 | 4 | |a TLR7 | |
| 650 | 4 | |a Type 1 diabetes | |
| 700 | 1 | |a Hopkinson, Jessica R |e verfasserin |4 aut | |
| 700 | 1 | |a Davies, Joanne |e verfasserin |4 aut | |
| 700 | 1 | |a Pearson, James A |e verfasserin |4 aut | |
| 700 | 1 | |a Leete, Pia |e verfasserin |4 aut | |
| 700 | 1 | |a Richardson, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Morgan, Noel G |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, F Susan |e verfasserin |4 aut | |
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